Two-photon microscopy allows for the visualization of cellular processes, such as cell migration, cell-to-cell and cell-to-matrix interactions, growth of tumors, microbial infection, and gene expression within the three- dimensional, natural environment of intact organs in living animals. During the past few years two-photon microscopy has revolutionized our view of developmental, homeostatic, and pathologic processes. We propose to establish an intravital two-photon microscopy system at The Wistar Institute through the acquisition of a Leica TCS SP2 Spectral Confocal and Two-Photon Microscope in combination with a Spectra-Physics Broadband Mai-Tai femtosecond-pulsed Laser. The major users of the proposed instrument will be a group of Wistar Investigators drawn from a wide range of disciplines, including immunology, tumor biology, skin biology, and infectious disease research. The need to translate experimental data from culture models into living animals, and to expand static information of dynamic cellular processes into four- dimensional kinetic .analyses in vivo has greatly augmented the need for intravital imaging at the Wistar Institute. Such research cannot be conducted by equipment currently available. Based on promising preliminary studies, the Investigators will explore in-depth the interactions between the immune system and tumor cells in vivo, immune cell interactions during inflammatory and infectious diseases, and melanocyte/melanoma cell behavior during tumor development and progression. The instrument will be centrally located at the Institute to enable convenient access for all users, will be managed by a dedicated instrument operator, and supervised by the Microscope Advisory Committee. Investigators from diverse fields will have new opportunities for interaction and the initiation of interdisciplinary research projects, which will significantly advance their NIH-funded projects. It is anticipated that the instrument will help to obtain novel insights into the pathomechanisms of disease, including autoimmunity, cancer, and chronic infections. [unreadable] [unreadable] [unreadable]